The goal of this project is to develop new diagnostic technology for detection and molecular analysis of cancer cells, especially circulating tumor cells. Our approach will be based on the previously developed DMR (diagnostic magnetic resonance) system that combines a miniaturized NMR probe with targeted magnetic nanoparticles for detection and molecular profiling of cancer cells. The system measures the transverse relaxation rate of water molecules in biological samples in which target cells of interest are labeled with magnetic nanoparticles. In preliminary study, we have detected a few cancer cells in fine needle aspirates, profiled the expression of cellular markers, and measured the pathway inhibition in small numbers of cancer cells. To further advance the DMR technology for molecular and cellular sensing of CTC, we propose three aims: 1) we will synthesize and further develop a new class of magnetic nanoparticles with high magnetic moments and optimize their chemical, biological properties for CTC labeling;2) we will implement a new DMR chip that can separate CTC from whole blood, measure multiple cancer markers in parallel, and sense the magnetic moments of individual cancer cells; 3) we will evaluate the clinical utility of the developed system using human samples, particularly detecting cancers outlined in the RFA (e.g. ovarian cancer, pancreatic cancer, glioma). Technology, materials and processes developed and optimized in this project will also be useful for Project 4 (implantable NMR based sensors), Projects 1 and 2 (targeting cancer cell populations) and Project 5 (novel hybrid nanomaterials).

Public Health Relevance

This proposal aims at optimizing, validating and further developing the most advanced magnetic nanotechnology for cellular analyses. The development and testing of a sensitive, reliable and robust platform for CTC detection, isolation and analysis has the potential to revolutionize cancer prevention and treatment.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA151884-03
Application #
8382475
Study Section
Special Emphasis Panel (ZCA1-GRB-S)
Project Start
Project End
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
3
Fiscal Year
2012
Total Cost
$400,363
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Kamaly, Nazila; Fredman, Gabrielle; Fojas, Jhalique Jane R et al. (2016) Targeted Interleukin-10 Nanotherapeutics Developed with a Microfluidic Chip Enhance Resolution of Inflammation in Advanced Atherosclerosis. ACS Nano 10:5280-92
Kamaly, Nazila; Yameen, Basit; Wu, Jun et al. (2016) Degradable Controlled-Release Polymers and Polymeric Nanoparticles: Mechanisms of Controlling Drug Release. Chem Rev 116:2602-63
Chertok, Beata; Langer, Robert; Anderson, Daniel G (2016) Spatial Control of Gene Expression by Nanocarriers Using Heparin Masking and Ultrasound-Targeted Microbubble Destruction. ACS Nano 10:7267-78
Liu, Yanlan; Gunda, Viswanath; Zhu, Xi et al. (2016) Theranostic near-infrared fluorescent nanoplatform for imaging and systemic siRNA delivery to metastatic anaplastic thyroid cancer. Proc Natl Acad Sci U S A 113:7750-5
Xu, Xiaoding; Wu, Jun; Liu, Yanlan et al. (2016) Ultra-pH-Responsive and Tumor-Penetrating Nanoplatform for Targeted siRNA Delivery with Robust Anti-Cancer Efficacy. Angew Chem Int Ed Engl 55:7091-4
Vegas, Arturo J; Veiseh, Omid; Doloff, Joshua C et al. (2016) Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates. Nat Biotechnol 34:345-52
Yu, Mikyung; Wu, Jun; Shi, Jinjun et al. (2016) Nanotechnology for protein delivery: Overview and perspectives. J Control Release 240:24-37
Yin, Hao; Song, Chun-Qing; Dorkin, Joseph R et al. (2016) Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo. Nat Biotechnol 34:328-33
Dang, Xiangnan; Gu, Li; Qi, Jifa et al. (2016) Layer-by-layer assembled fluorescent probes in the second near-infrared window for systemic delivery and detection of ovarian cancer. Proc Natl Acad Sci U S A 113:5179-84
Cui, Jian; Beyler, Andrew P; Coropceanu, Igor et al. (2016) Evolution of the Single-Nanocrystal Photoluminescence Linewidth with Size and Shell: Implications for Exciton-Phonon Coupling and the Optimization of Spectral Linewidths. Nano Lett 16:289-96

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